Quaternary ammonium salts of sulfur bearing anions



United States Patent Ofitice Patented Mar. 28, 1967 This invention relates to relatively water-insoluble, microbiologically active compounds, and it more particularly relates to quaternary ammonium thio compounds of the aforesaid type.

This is a continuation-in-part of applicants co-pending application Ser. No. 352,638, filed Mar. 17, 1964, now abandoned.

In accordance with the present invention, the compounds are formed by the reaction of certain water-soluble quaternary ammonium compounds, either as their hydroxides or their salts of inorganic acids, with organic aliphatic bivalent sulfur-bearing compounds of the class consisting of thio alcohols, thio acids and thio ethers. Typical of these thio compounds are octyl mercaptan, decyl mercaptan, lauryl mercaptan, thioglycolic acid, dithioglycolic acid and t-dodecyl thioglycolic acid. The quaternary ammonium compounds used in the process of this invention have a phenol coefficient of at least 100 with respect to both Staphylococcus aureus and Salmonella typhus at 20 C. and contain at least one carbon chain having from 8 to 22 carbon atoms. Furthermore, the quaternary nitrogen atom may be a member of a heterocyclic ring such as pyridine, isoquinoline, morpholine or pyrrolidine, if desired.

Typical examples of these quaternary ammonium compounds are alkyl trimethyl'ammonium chlorides, alkylbenzyl trimethyl ammonium chlorides, alkyl dimethyl benzyl ammonium chlorides, alkyl dimethyl menaphthyl ammonium chlorides, alkyl dimethyl substituted-benzyl ammonium chlorides in which the benzyl radical is substituted with one or more side chains containing from 1 to 5 carbon atoms such, for example, as methyl, dimethyl, ethyl, amyl and the like and in which the carbon atoms may all be in the same or different side chains, or in which the benzyl radical bears one, two or more halogen atoms such as chlorine or bromine, alkyl pyridinium chlorides, alkyl lower-alkyl pyrrolidinium chlorides, alkyl isoquinilinium chlorides or bromides, alkyl loWer-alkyl morpholinium chlorides, in all of which the alkyl group may have from 8 to 22 carbon atoms and the lower alkyl group may have from 1 to 4 carbon atoms, and alkyl phenoxy ethoxy ethyl dimethyl benzyl ammonium chloride in which the alkyl radical may be iso-octyl or nonyl and in which the phenyl radical may, if desired, have a methyl substituent thereon. Various other analogs of these quaternaries may also be employed such, for example, as cetyl dimethyl ethyl ammonium bromide or oleyl dimethyl ethyl ammonium bromide. In all instances, however, it is to be noted that there must be one higher alkyl group of from 8 to 22 carbon atoms attached to the nitrogen. This is necessary in order to produce thio reaction products which have the necessary degree of germicidal activity and water-insolubility.

It has generally been thought that water-soluble quaternary ammonium salts such, for example, as those of the preceding types which are microbiologically active, lose their microbiological activity when reacted with materials which render them water-insoluble. It has, however, now been discovered that, contrary to general belief,

the reaction of such microbiologically active, water-soluble quaternary ammonium compounds of the aforesaid type with either aliphatic thio alcohols, thio acids or thio ether-s, or with water-soluble salts of the same, yield products which are substantially water-insoluble and yet are, in many cases, as active microbiologically as the parent quaternary ammonium compounds from which they are derived. In many cases, they are more active.

Exemplifying the type of compounds embodying the present invention are the following:

Octyl mercaptan C H SH.

Decyl mercartan C H SH.

Lauryl mercaptan C I-1 811. Thioglycolic acid HSCH COOH. Thiodiglycolic acid S(CH COOH) t-Dodecyl thioglycolic acid (C H )SCH COOH.

The compounds of this invention may be prepared by mixing aqueous solutions of the quaternary ammonium salts or hydroxides with an aqueous solution of the thio compound or its water-soluble salts.

After thorough mixing, the organic product layer is separated from the aqueous layer (as with a separatory funnel) since two distinct phases are formed. Separation may be facilitated by the addition of an organic solvent immiscible with water. The product layer may be washed with water to remove any residual by-product salt or unreacted materials. The solvent, if any, may be evaporated and the product air or vacuum dried to a paste, wax, oil 'or solid.

It is not necessary to use an aqueous medium. Any solvent or solvent mixture in which the starting materials are soluble will be satisfactory. Non-aqueous solvents facilitate the separation of the by-product inorganic salt and reduce the need for vacuum drying to get an anhydrous product. When a non-aqueous medium is employed, it is usually necessary to add a small amount of water to facilitate ionic reaction.

The product may be used, if desired, without drying since any entrapped water is irrelevant to the microbiological activity of the compounds. In other applications, removal of water may be essential for reasons not related to biological activity.

An alternative method for the preparation of compounds especially applicable to the treatment of fabric, ropes, net, woven and non-woven fabric and reticulated or convoluted materials, involves a two-step process. In the first step, the material is passed through a bath containing the anionic moiety. Excess solution is removed by methods well known to those skilled in the art. The treated material is then passed through a second bath wherein the concentration of quaternary ammonium compound is such that the material picku will result in an equivalent amount of quaternary ammonium compound reacting with the anionic moiety, depositing the product in the most intimate way on the surface and in the interstices, convolutions and reticulations of the material.

The method of adjustment of solution concentration to achieve the required pickup is well known to those skilled in the art. The order of treatment may be reversed without affecting the biological activity or durability of the product on the material. The products of this invention may be formulated as water dispersions by dissolving them in a water-miscible organic solvent such as acetone or methanol and diluting with water or by dissolving them in emulsifiable oils such, for example, as sulfonated castor oil or pine oil and diluting with water. In preparing aqueous dispersions, emulsifying agents such, for example, as ethylene oxide condensates of alkyl phenols may be used with or without organic solvents.

It is surprising that the compounds of this invention exhibit high microbiological activity despite their relative insolubility in water. Because of their unusual combination of physical and microbiological properties, they can be used to impart laundry-resistant, anti-microbial characteristics to textiles. They can also be used as the active agent in anti-mildew finishes for textiles which are resistant to leaching.

Although the compounds have low water solubility, they are compatible with various organic solvents, plasticizers and high molecular weight compounds. Consequently, they may be incorporated as anti-microbial agents in synthetic resins and plastics. The compounds are compatible with natural and synthetic rubber latices. Therefore, they may be used to prepare bacteriostatic films and molded objects deposited from such latices.

The compounds can be incorporated into cutting and grinding fluids without precipitation. Also, they blend well with nonionic and anionic surface active agents. In such compositions they retain their microbiological activity.

It will be understood that the properties of the products described herein will vary depending upon the nature of the cationic quaternary ammonium compound used in their preparation as well as the anionic compound reacted therewith.

The chemical, physical and biological properties of the products of our invention make them especially appropriate for the following applications when suitably incorporated in active amounts in an appropriate vehicle, binder, medium or substrate:

(1) Mildewproofing fabric, canvas, ropes, textiles, awnings, sails, tenting and other Woven and non-woven reticulated materials.

(2) Paint mildewstats.

(3) Jet plane fuel additive to control growth of microorganisms.

(4) Odor preservative agents for clothes and shoes.

(5) Mildew retardant and odor suppressant for shoes and other leather products.

(6) Topical antiseptics.

(7) Antidandrufi agents.

(8) Disinfection agents for hair and gut of man and beast.

(9) Bacteriostatic furniture dressing.

(10) Surface finishes for stone, plaster, tile, cement, brick and other inorganic building materials to retard growth of microorganisms, fungi, mold and algae.

(11) Wool preservative.

(12) Plant and tree spray to combat fungi.

(13) Antimycotic agents for soap Wrappers.

(14) Self-sanitizing brushes.

(15) Mildewproofing agent in and on plastic and film.

(16) Mildewproofing of cellulosics, cardboard, fibreboard, paper and cordage.

(17) Contact biostat for application to film, waxes and cloth to preserve cheese, meats and vegetables and other food products.

(18) Algae inhibition, especially on surfaces and in solution where low foaming is desirable.

(19) Paper pulp slime control.

(20) Sanitizing agent for rug, carpet, curtains.

(21) Egg preservation.

(22) Adhesive preservation.

(23) Preservation of latex paints.

(24) Preservation of metal-Working compounds.

(25) Additives for soap and for both anionic and nonionic detergents in liquid, bar, powder, bead, solution and other forms to impart bacteriostatic and fungistatic properties thereto.

The microbiological activity of our compounds has been evaluated for microbiological stasis by the Standard of applications, the inhibition of growth rather than out= right kill is satisfactory,

Briefly put, the Tube Dilution Test consists in placing 9 cc. of the CSMA Broth in a test tube which is then sterilized in an autoclave. One cc. solution of the micro= biologically active compound at an appropriate concen-' tration is added to the test tube which is then inoculated with 0.1 cc. of a twenty-four hour old culture of the organism under study. The test tube is then incubated at 370 C. for forty-eight hours and observed for bacterial growth.

The same procedure is followed for fungi. In such tests, however, the tubes are incubated for fourteen days at a temperature suitable for optimum fungal growth, usually 25 C.

The invention is illustrated by, but not restricted to, the following examples:

Example 1 To m. of a 0.30 M solution of sodium lauryl mer captide of molecular weight 224 in a separatory funnel was added 90 ml. of a 0.315 N solution of alkyl dimethyl benzyl ammonium chloride, average molecular weight 380 (technical grade, wherein alkyl=C 60%, C 2 30%, C 5%, C 5%; Onyx Chemical Corporations ETC-824). The funnel was agitated vigorously and a little benzene was added to facilitate layer separation. A colorless oily layer was separated and dried in a vac uum oven. 14.7 grams of a yellow paste was obtained at a yield of of the theoretical of alkyl dimethyl benzyl ammonium lauryl mercaptide.

Example 2 94 ml. of a solution containing 0.0344 equivalents of the sodium salt of tert-dodecyl thiogylcolic acid of equiva' lent weight 282 and 129 ml. of a solution of alkyl di methyl ethylbenzyl ammonium chloride containing 0.0344 equivalents were mixed in a separatory funnel by vigor ous shaking. A little benzene was added to facilitate layer separation and the brine was tapped off. The oil? layer was vacuum dried to yield 21 grams of a viscous yellow liquid at 102% of the theoretical yield of alkyl dimethyl ethyl-benzyl tert-dodecyl thioglycolate.

Example 3 The disodium salt of thioglycolic acid was prepared in "1.09 molar aqueous solution. To 50 ml. of this was added 420 ml. of a 0.261 normal solution of lauryl isoquinohnium bromide in a water-isopropanol medium. On evaporating until the alcohol was removed, a red oil was obtained along with a solution of sodium bromide. This was separated in a separatory funnel. The oil was dried and yielded 86% of the theoretical weight of the dilauryl isoquinolinium salt of thioglycolic acid.

Example 4 By procedures similar to those described in Examples 1 to 3, quaternary ammonium salts of octyl mercaptan, decyl mercaptan and thiodiglycolic acid were prepared in yields approximating the theoretical, by reacting solutions of their sodium salts with solutions of alkyl dimethyl benzyl ammonium chloride, alkyl dimethyl ethylbenzyl ammonium chloride, and lauryl isoquinolinium bromide, to produce the corresponding quaternary ammonium salts of the respective thio compounds.

Example 5 The results of static dilution tests performed on prodnets of Examples 1 to 4 are shown in the following table:

BACTERIOSTATIC ACTIVITY OF VARIOUS QUATE RNARY AMMONIUM SALTS OF THlO-ACIDS-ALOOHOLS AND EIHERS Reciprocal of Static Dilution Level of Product vs.-

Quaternary Acid Staph-y- Salmo- Aspar- Zococcus nella gillua aureus typhosa m'ger Alkyl Dirnethyl Ethyl-Benzyl Ammo- Decyl Mercaptan 10 10 nium Chloride. Lauryl Mercaptan 10 10 10 Tert-Dodecyl Thioglyco A 10 10 10' Thioglycolic Acid 10 10' 10 Alkyl Dimethyl Benzyl Ammonium Deeyl Mercaptan 10 10 10 Chloride. Lauryl Mercaptan 10 10 10 T-Dodecyl Thioglycolic Acid 10 10 10 Lauryl Isoquiuolinium Bromide Lauryl Mercaptuu 10 10* 10 Thioglycolic Acid 10 10 10 Thiodiglycolic Acid 10 10 10 T-Dodecyl Thioglycolic Acid 10 10 10 Obviously, many modifications of the present invention are possible in the light of the above teachings. It is, therefore, to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described.

The invention claimed is:

1. A quaternary ammonium salt of an aliphatic bivalent sulfur-bearing compound wherein the quaternary ammonium cation has at least one alkyl group of from 8 to 22 carbon atoms attached to the nitrogen and possesses a phenol coefiicient of at least 100 with respect to both Staphylococcus aureus and Salmonella typhus at C., and wherein the sulfur-bearing anion is furnished by a member selected from the group consisting of a higher alkyl mercaptan, thioglycolic acid, thiodiglycolic acid and t-dodecyl thioglycolic acid.

2. The compound of claim 1 wherein the quaternary ammonium cation is a member of the group consisting of alkyl trimethyl ammonium, alkyl benzyl trimethyl ammonium, alkyl dimethyl benzyl ammonium, alkyl dimethyl menaphthyl ammonium, alkyl dimethyl benzyl ammonium in which the benzyl is substituted by at least one alkyl of from 1 to 5 carbon atoms, alkyl dimethyl halo-substituted benzyl, alkyl pyridinium, alkyl lower alkyl pyrrolidinium, alkyl isoquinolinium, alkyl lower alkyl morpholinium, alkyl phenoxy ethoxy ethyl dimethyl benzyl ammonium, cetyl dimethyl ethyl ammonium and oleyl dimethyl ethyl ammonium, the term alkyl referring to an alkyl having from 8 to 22 carbon atoms and the term lower alkyl referring to an alkyl having from 1 to 4 carbon atoms.

3. The compound of claim 1 wherein the anion is the residue of octyl mercaptan.

4. The compound of claim 1 wherein the anion is the residue of decyl mercaptan.

5. The compound of claim 1 wherein the anion is the residue of lauryl mercaptan.

6. The compound of claim 1 wherein the anion is the residue of thioglycolic acid.

7. The compound of claim 1 wherein the anion is the residue of thiodiglycolic acid.

8. The compound of claim 1 wherein the anion is the residue of t-dodecyl thioglycolic acid.

References Cited by the Examiner FOREIGN PATENTS 1/1961 Great Britain. 3/1961 Great Britain. 

1. A QUATERNARY AMMONIUM SALT OF AN ALIPHATIC BIVALENT SULFUR-BEARING COMPOUND WHEREIN THE QUATERNARY AMMONIUM CATION HAS AT LEAST ONE ALKYL GROUP OF FROM 8 TO 22 CARBON ATOMS ATTACHED TO THE NITROGEN AND POSSESSES A PHENOL COEFFICIENT OF AT LEAST 100 WITH RESPECT TO BOTH STAPHYLOCOCCUS AUREUS AND SALMONELLA TYPHUS AT 20*C., AND WHEREIN THE SULFUR-BEARING ANION IS FURNISHED BY A MEMBER SELECTED FROM THE GROUP CONSISTING OF A HIGHER ALKYL MERCAPTAN, THIOGYCOLIC ACID, THIODIGYLCOLIC ACID AND T-DODECYL THIOGYLCOLIC ACID. 